Critical Appraisal DR Joshna Rajbaran. CARDIAC TROPONIN and OUTCOME in ACUTE HEART FAILURE NEJM...

Critical Appraisal

DR Joshna Rajbaran

CARDIAC TROPONIN and OUTCOME in ACUTE HEART

FAILURENEJM 358;20 MAY 15,2008

THE AIM:

• To describe the association between elevated cardiac troponin levels and adverse events in hospitalized patients with ACUTE DECOMPENSATED HEART FAILURE

WHY??

• Because an objective risk-stratification process for the evaluation of acute decompensated heart failure is lacking.

• The value of measuring serum cardiac troponin when a patient presents with acute decompensated heart failure remains uncertain.

NB: Troponins

• Trop T & Trop I are regulatory proteins with a very high specificity for cardiac injury . They are released early ( 2-4 hrs) & can persist for up to 7 days.

• Troponin testing is primarily used as a tool in diagnosing myocardial infarctions.

• Elevated levels suggest myocardial or some form of cardiac damage.

• Insignificant if used in the absence of S&S of cardiac disease!!

THE KEY DIFFERENCES

• LARGE STUDY

• SHORT TERM OUTCOMES

• IN HOSPITALIZED PATIENTS WITH ACUTE DECOMPENSATED HEART FAILURE.

METHOD

• Registry data:–ADHERE( Acute Decompensated

Heart Failure National Registry)–Observational registry–274 hospitals–TIME FRAME :October 2001 January 2004

Inclusion criteria:Hospitalization & documentation

of the measurement of trop I or trop T at “INITIAL” evaluation

Exclusion criteria: serum creatinine level>2.0mg/dl or 176.8umol/lIschemic heart failure defined as

cause if : hx coronary artery disease OR hx myocardial infarction Not as exclusion criteria!!!

METHOD

• Troponin measurement:Trop T & trop I were

interchangeable levels considered positive, with cut-off based on expert consensus!!

Trop T≥0.1µg/l & Trop I ≥1.0µg/l

Method

• Statistical analysis:Primary out-come all causesSecondary out-come differences

in medical mx / procedures / length of stay between +ve & -ve cohorts

All outcomes were specified before the data were examined

• Statistical analysis ( cont)Associations between therapy

& mortalityControls used in this regardMortality was adjusted for

relevant prognostic factors

Logistic regression adjusted for:

age / blood urea nitrogen / SBP /

DBP / serum creatinine / serum sodium / HR /dyspnea at rest

1.2% records excluded due to missing values

SAS softwareStudy designed by all authorsADHERE statisticians

METHOD

SourceTime periodInclusion criteriaExclusion criteriaIHD/Race / Gender

troponin measurements justified

Statistical analysis explained

Tools and teams stated

RESULTS

• Troponin levels & characterists of the patients

105,388 84,872 ( 80.5% )

Hospitalized Trop tested

Cr < 2mg/dl

67,924

Positive Negative

4240 (6,2%) 63,684

• There were small but significant differences between the two cohorts!!!

• Troponin- positive patients on admission:

Lower SBPLower EFLess likely AFSummary of characteristics given +ve

vs –ve TropNo comparison made for the two

proteins as only 2% had both tested!!

REVISION OF TERMINOLOGY

• Odds ratio :provides a more useful way of presenting diagnostic data & can be applied to individual patients in a way that specificity & sensitivity cannot . It is a number btw 0 to infinity IF > 1 indicates that the information increases the likelihood of the suspected diagnoses. IF <1 it decreases the likelihood of the suspected diagnoses!!

• SPECIFICITY: the proportion of patients WITHOUT the disease who are correctly identified by the test.

• SENSITIVITY: the proportion of patients WITH the disease who are correctly identified by the test.

RESULTS

• In-hospital mortalityTrop Positive (8.0%) > Trop

Negative (2.7%) patients.......... (P<0.001)

Actuarial analysisTrop as a continuous variableAdjusted odds ratio for death

(P<0.001)

IHF was not a useful discriminator of Troponin status, nor was it predictive of mortality.

IHF Trop +ve 53% Trop –ve 52%Trop +ve mortality 8,4% IHF 7,4% non-IHFTrop –ve mortality 2,8% IHF 2,6% non-IHF

RESULTS

• Treatment , Troponin status & MortalityDiuretics+ve more likely to receive: nitroglycerine ,

inotropes & vasodilatorsResource utilization and mortalityNo interaction between treatment &

Troponin status with respect to mortality

RESULTS

Sample size large but justifiedBasic data adequately describedVariables taken into accountMissing data accounted forNumbers add upHigh risk cohort establishedStatistical significance assessed

Main findings and their value:

Prognostic value / cost Early assessment of risk/ triage & management Add to existing risk-stratification data for predicting

the short term risk of death among patients with acute decompensated heart failure... Blood urea>15.4mmol/l

SBP < 115mm Hg Cr >243.1µmol/l More aggressive therapeutic approach justified

Value of findings from Trop negative cohort Identifying low risk patients/ planning Rx Other studies the impact of early risk stratification

has been supported BASEL TRIAL EFFECT STUDY SMALLER STUDIES-98 CONSECUTIVE

PTS -159 PTS -RITZ-4 STUDY

Studies correlating Troponin with physiological variables

Impact on guidelines : National-ACS Trop & brain natriuretic

peptide or N- terminal pro-brain peptide. Current for Heart Failure Trop NOT

mentioned & brain nitriuretic peptide only if dx uncertain!!!

• Suggested guideline!!!

• Measurement of Troponin levels in patients who present with heart failure provides independent prognostic information regarding in hospital death & other clinical outcomes & can be useful for risk stratification of such patients!!!!

LIMITATIONS

• Retrospective analysis• ADHERE large data set : investigator

discretion , diagnosis not objectively ascertained , cause of death not consistently recorded

• Troponin testsIntroduction of variability/ biasMeasurement only at admissionInteraction with other biomarkers• Under represented adverse outcomes

Critical appraisal

• INFORMATIVE STUDY • AIM/METHOD/FINDINGS• SIGNIFICANCE• STRENGTHS & LIMITATIONS WITH

SUGGESTIONS OFFERED• I FOUND NO REASON TO QUESTION THE

STATISTICAL APPROACH• SUGGESTIONS FOR FUTURE STUDIES• OTHER RELEVANT STUDIES

DOCUMENTED

With relevance to SA

• South African statistics :10 473 mortalities per annum d/t Heart Failure vs. US 55,704

• Further evaluation of other biomarkers vs Trop T required

• Cost factors need to be examined

• Ischaemic heart disease is the commonest cause for acute heart failure in America.

• HOWEVER, in Sub- Saharan Africa the causes in Africans are largely ( > 90%) NON-ISCHAEMIC viz.:

HPT / cardiomyopathy / Rheumatic heart disease / chronic lung disease / pericardial disease

• Coronary artery disease and it’s complications remain uncommon in Africa but the situation is changing!!

• I found the journal article rather transparent in it’s limitations

• However, there was one limitation that seemed to stand out:

that some patients with both heart failure and ACS may have been included!!!!

• I think that with urbanization ,varying risk profiles amongst race groups , risk prone behaviour & diet, that the findings are worthy of consideration in our setting.

• Finally , EARLY RISK STRATIFICATION may help identify patients who are likely to receive the greatest benefit from intensive therapy.....that in itself highlights it’s relevance to emergency medicine!!!!